Genotyping and Genetic Epidemiology. The CIP Genetics Core (CIPGC) has been active in both the generation of genotypic data and in the statistical, bioinformatic and epidemiological analysis of the genetic data. In particular, the work of the Genetics Core over the past year has been used by CIP principal investigators to establish findings for 2 published manuscripts. The CIPGC participated in the study of genetic factors involved in the control of HIV viral load. Manuscripts identified genomic locations in the human genome of major effects in such control. In particular, a region of the 3 untranslated region of the HLA-C gene is targeted by a microRNA resulting in reduced expression of the gene and higher human immunodeficiency virus (HIV) viral loads. We are supporting research investigating the mechanism by which polymorphism in the target site of the microRNA arise and how this affects outcomes in HIV disease. We have been involved in analysis of HLA-C genomic sequences that enabled us to identify the polymorphisms of the binding site and the donor sequence involved in gene conversion at the site, resulting in 2 publications. Additionally we are using bioinformatic analyses to characterize possible roles for this polymorphism of HLA-C and other MHC genes in transplantation outcomes. Following our involvement in implicating polymorphisms in IL28B in HCV clearance in humans, we have characterized the IL28B gene in chimpanzees in order to identify the specific polymorphism directly responsible for HCV clearance. An additional publication involves the characterization of the role of transporter genes in multidrug resistance in cancer stem cells. We are characterizing the sequence and recombinational characteristics as well as integration sites of mouse retroviruses that are derived from endogenous sequences and associated with the generation of thymic lymphoma and initiating work into the role of the microbiome in control of inflammation in this system.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Scientific Cores Intramural Research (ZIC)
Project #
1ZICBC011237-05
Application #
8763768
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
5
Fiscal Year
2013
Total Cost
$904,241
Indirect Cost
Name
National Cancer Institute Division of Basic Sciences
Department
Type
DUNS #
City
State
Country
Zip Code
Ramsuran, Veron; Kulkarni, Smita; O'huigin, Colm et al. (2015) Epigenetic regulation of differential HLA-A allelic expression levels. Hum Mol Genet 24:4268-75
Lou, Hong; Villagran, Guillermo; Boland, Joseph F et al. (2015) Genome Analysis of Latin American Cervical Cancer: Frequent Activation of the PIK3CA Pathway. Clin Cancer Res 21:5360-70
Petersdorf, Effie W; Gooley, Theodore A; Malkki, Mari et al. (2014) HLA-C expression levels define permissible mismatches in hematopoietic cell transplantation. Blood 124:3996-4003
Rizvi, Syed Monem; Salam, Nasir; Geng, Jie et al. (2014) Distinct assembly profiles of HLA-B molecules. J Immunol 192:4967-76
Bashirova, Arman A; Martin-Gayo, Enrique; Jones, Des C et al. (2014) LILRB2 interaction with HLA class I correlates with control of HIV-1 infection. PLoS Genet 10:e1004196
Dean, Michael; Bendfeldt, Giovana; Lou, Hong et al. (2014) Increased incidence and disparity of diagnosis of retinoblastoma patients in Guatemala. Cancer Lett 351:59-63
Dean, Michael; Lou, Hong (2013) Genetics and genomics of prostate cancer. Asian J Androl 15:309-13
Ranasinghe, Srinika; Cutler, Sam; Davis, Isaiah et al. (2013) Association of HLA-DRB1-restricted CD4⁺ T cell responses with HIV immune control. Nat Med 19:930-3
McLaren, Paul J; Coulonges, Cédric; Ripke, Stephan et al. (2013) Association study of common genetic variants and HIV-1 acquisition in 6,300 infected cases and 7,200 controls. PLoS Pathog 9:e1003515
Jiménez-Morales, Silvia; Martínez-Aguilar, Nora; Gamboa-Becerra, Roberto et al. (2013) Polymorphisms in metalloproteinase-9 are associated with the risk for asthma in Mexican pediatric patients. Hum Immunol 74:998-1002

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